An Efficacy and Safety Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine in Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML) and Low-Blast Acute Myelogenous Leukemia (AML)

Inclusion Criteria

• Male or female participants 18 years or older.
• Morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cells [WBC] =5%.
• WHO defined AML with 20% to 30% myeloblasts in the bone marrow and 6 points),
• High (>4.5 to 6 points), or
• Intermediate (>3 to 4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Clinical laboratory values within the following parameters (repeat within 3 days before the first dose of study drug if laboratory values used for randomization were obtained more than 3 days before the first dose of study drug):
• Albumin >2.7 g/dL.
• Total bilirubin =50 milliliter per minutes (mL/min).
• Hb >8 g/dL. Participants may be transfused to achieve this value. Elevated indirect bilirubin due to post transfusion hemolysis is allowed.
• For CMML participants: WBC count 1.5 ULN or active uncontrolled coagulopathy or bleeding disorder.
• Known human immunodeficiency virus (HIV) seropositive.
• Known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (that is, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
• Known hepatic cirrhosis or severe pre-existing hepatic impairment.
• Known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association [NYHA] Class III or IV) and/or myocardial infarction within 6 months prior to first dose, or severe pulmonary hypertension. As an example, well controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion.
• Treatment with strong cytochrome P450 (CYP) 3A inhibitors or inducers within 14 days before the first dose of study drug.
• Systemic antineoplastic therapy or radiotherapy for other malignant conditions within 12 months before the first dose of any study drug, except for hydroxyurea.
• Female participants who are lactating and breast feeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
• Female participants who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
• Male participants who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).